Efficacy and safety of medical therapy for low bone mineral density in patients with inflammatory bowel disease: a meta-analysis and systematic review

Clin Gastroenterol Hepatol. 2014 Jan;12(1):32-44.e5. doi: 10.1016/j.cgh.2013.08.024. Epub 2013 Aug 24.


Background & aims: Patients with inflammatory bowel disease (IBD) are at risk for osteoporosis and fracture. However, the efficacy of medical treatments for osteoporosis in increasing bone mineral density (BMD) in patients with IBD has not been well characterized.

Methods: We conducted a meta-analysis and systematic review of controlled trials to evaluate the efficacy and safety of medical therapies used for low BMD in patients with IBD (Crohn's disease, ulcerative colitis, or indeterminate colitis). We searched MEDLINE, EMBASE, Google scholar, the University Hospital Medical Information Network (UMIN) Clinical Trials Registry, and Cochrane Central Register of Controlled Trials for studies that assessed the efficacy of medical treatment for low BMD in patients with IBD. We also manually searched abstracts from scientific meetings and bibliographies of identified articles for additional references. The primary outcome assessed was changes in BMD at the lumbar spine. We also collected data on hip BMD, numbers of new fractures, and adverse effects. Data were pooled by using random-effects models and by mixed-effects analysis for primary aims, when subgroup analysis by individual drug was possible.

Results: We analyzed data from 19 randomized controlled studies; 2 used calcium and vitamin D as therapies, 13 used bisphosphonates, 4 used fluoride, 1 used calcitonin, and 1 used low-impact exercise. The pooled effect of bisphosphonates was greater than that of controls in increasing BMD at the lumbar spine (standard difference in means, 0.51; 95% confidence interval, 0.29-0.72) and hip (standard difference in means, 0.26; 95% confidence interval, 0.04-0.49) with comparable tolerability, and the risk of vertebral fractures was reduced. Fluoride increased lumbar spine BMD, but its ability to reduce risk of fracture was unclear. There was no evidence that the other interventions increased BMD.

Conclusions: On the basis of a meta-analysis, bisphosphonate is effective and well tolerated for the treatment of low BMD in patients with IBD and reduces the risk of vertebral fractures. There are insufficient data to support the efficacy of calcium and vitamin D, fluoride, calcitonin, or low-impact exercise. However, the small number of randomized controlled trials limited our meta-analysis.

Keywords: BMD; CD; CI; Clinical Trial; Crohn's disease; Estrogen; GC; IBD; OR; Osteopenia; SDm; UC; bone mineral density; confidence interval; glucocorticoid; inflammatory bowel disease; odds ratio; standard difference in means; ulcerative colitis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Controlled Clinical Trials as Topic
  • Diphosphonates / adverse effects
  • Diphosphonates / therapeutic use*
  • Fractures, Bone / prevention & control
  • Humans
  • Inflammatory Bowel Diseases / complications*
  • Osteoporosis / drug therapy*
  • Treatment Outcome


  • Bone Density Conservation Agents
  • Diphosphonates